Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection.

In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 (47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 ± 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 ± 0.26 and 2.25 ± 0.28, respectively) compared with explanted allografts without antibody-mediated rejection (0.42 ± 0.11 and 0.36 ± 0.09, p = 0.046 and p < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure.

Adapted treatment of Epstein-Barr virus infection to prevent posttransplant lymphoproliferative disorder after heart transplantation.

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.

Who gets a second heart? A current picture of cardiac retransplantation.

BACKGROUND: Heart retransplantation (HRT) accounts for 2.6% of heart transplantation (HT) indications. We performed a retrospective analysis of our recent HRT experience. METHODS: From January 2000 to June 2012, 820 HTs were performed; 798 (97.3%) were primary HTs and 21 (2.5%) 2nd HTs. Indications for HRT included: 57% cardiac allograft vasculopathy, 33% nonspecific graft failure, 5% primary graft failure (PGF), and 5% refractory acute rejection. The primary outcome was overall survival. Our results were compared with the most representative publications reporting HRT experiences before January 2000. RESULTS: Mean age at HRT was 39.9 ± 14.3 years, and there was a predominance of male patients (62%). Overall mortality was 52%; 30-day mortality was 19%. Eight patients (38%) developed PGF after HRT and 3 of them (38%) died within 30 days. Overall actuarial survivals at 1 month and 1, 3, and 5 years were 81.0%, 70.8%, 59.9%, and 53.3%, respectively. No significant risk factors for mortality could be identified. CONCLUSIONS: We observed improved short- and medium-term survival after HRT. This finding is probably related to changing recipient profiles, with less patients being retransplanted for PGF and more patients undergoing late retransplantation. Higher rates of PGF after HRT reflect our efforts to broaden the allograft pool by using marginal donors.

Human herpesvirus 8 (HHV8) transmission and related morbidity in organ recipients.

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2-year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow-up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8-related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.

[Etiology of ecthyma gangrenosum: four cases]. / Etiologie de l'ecthyma gangréneux (quatre cas).

INTRODUCTION: Ecthyma gangrenosum (EG) starts as an erythematous or purpuric macule, papule or plaque that develops into a haemorrhagic bulla, which becomes a necrotic black sore. EG is usually a cutaneous manifestation of Pseudomonas aeruginosa infection but other microbial agents can be involved. OBSERVATION: Four patients (three women and one man, mean age: 36 years) with fever and cutaneous black sores characteristic of EG were hospitalized. Three were cardiac transplant recipients treated with immunosuppressant drugs and one had end-stage acute myeloid leukaemia. All had cutaneous necrotic black sores. Blood cultures isolated in one case P. aeruginosa and Candida albicans. Bacteriological culture of cutaneous swabs from necrotic lesions revealed C. albicans and P. aeruginosa in two cases, respectively. The cutaneous black sores healed with appropriate antimicrobial treatment. Three patients were cured but the patient with leukaemia died despite therapy. DISCUSSION: These four cases illustrate the clinical polymorphism of EG and the broad spectrum of aetiologies. While EG is primarily considered a cutaneous manifestation of P. aeruginosa infection, other microbial agents such as C. albicans may be responsible, as in two of our cases.

Results after orthotopic heart transplantation accepting donor hearts >50 years: experience at La Pitie Salpetriere, Paris.

INTRODUCTION: We sought to examine the results of orthotopic heart transplantation accepting hearts from donors >50 years of age with special regard to the usefulness of peripheral extracorporeal membrane oxygenation for posttransplant graft dysfunction. PATIENTS: Between January 2000 and December 2004, a total of 247 patients underwent orthotopic heart transplantation. In 143 patients (58%) the heart donor was <50 years (group I, mean age of donor hearts 36 +/- 11 years; range, 8-49 years). In 104 recipients (42%) the heart donor was >50 years (group II, mean age of donor hearts 56 +/- 15 years; range, 50-67 years). Pretransplant characteristics of the two groups showed no significant differences. RESULTS: The in-hospital mortality was slightly increased in group II (24% vs 20% in group I, NS) and the 5-year survival rate significantly increased in group I (75% vs 63% in group II). Freedom from transplant vasculopathy after 3 years was similar in both groups (86% in group I vs 87% in group II). A total of 25 patients (17%) in group I and 27 patients (26%) in group II developed graft dysfunction. Eleven patients in group I and 10 patients in group II were treated using peripheral extracorporeal membrane oxygenation, whereas 3 of the 11 patients in group I and 5 of the 10 patients in group II were discharged following a complete recovery. Two patients in group I and 4 patients in group II were survivors beyond year. CONCLUSION: In our experience it was possible to increase the cardiac donor pool by accepting allografts from donors >50 years of age in selected cases. The incidence of transplant vasculopathy was not increased, whereas in-hospital mortality was slightly higher. In our limited cohort, patients with older donor hearts was developed graft dysfunction profited from primary extracorporeal membrane oxygenation implantation, an indication that should be examined further without delay.

[Annuloplasty reduces the mitral leaflets mobility]. / L'annuloplastie réduit la mobilité des deux feuillets mitraux.

The posterior mitral leaflet is usually motionless following mitral valve repair. The aim of this study was to assess (1) the geometric changes of the left ventricular base following prosthetic ring annuloplasty and (2) their impact on the anterior mitral leaflet (AML) mobility. Thirty five patients operated upon for mitral valve repair underwent an intraoperative transesophageal echographic study before and after annuloplasty. A posterior leaflet resection was achieved in 29 cases and ring annuloplasty alone in 6 cases. No repair technique was performed on the AML. Four parameters were assessed: the anteroposterior mitral annulus diameter, the aortomitral angle, the opening and closure angles of the AML. Annuloplasty resulted in a drastic reduction of the mitral annulus from 36.8 +/- 5.6 mm to 20.9 +/- 3.8 mm (systole, long axis view) (p < 0.0001). The aortomitral angle decreased following annuloplasty from 115.1 +/- 8.3 to 108.0 +/- 9.60 (systole, long axis view) (p < 0.0001). No difference was observed between systolic and diastolic measurments concerning the mitral annulus or the aortomitral angle. The opening angle of the AML remained unchanged whereas the closure angle increased from 17.8 +/- 6.10 to 26.6 +/- 6.70 (long axis view) (p = 0.0001) resulting in a displacement of the coaptation point towards the apex. Consequently, the excursion of the anterior leaflet throughout the cardiac cycle decreased following annuloplasty from 43 +/- 130 to 32.5 +/- 11 (long axis view) (p < 0.0001).

[Pseudo-aneurysms of the ascending aorta in patients previously operated for acute aortic dissection]. / Pseudo-anévrismes de l'aorte ascendante chez les patients déjà opérés d'une dissection aortique aiguë. Diagnostic, traitement.

Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.